title: Non-overlapping activities of ADF and cofilin-1 during the migration of metastatic breast tumor cells.
abstract: BACKGROUND
  ADF/cofilin proteins are key modulators of actin dynamics in metastasis and invasion of cancer cells. Here we focused on the roles of ADF and cofilin-1 individually in the development of polarized migration of rat mammary adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein. Small interference RNA (siRNA) technology was used to knockdown (KD) the expression of ADF and cofilin-1 independently.
  
  
  RESULTS
  Either ADF KD or cofilin KD caused cell elongation, a reduction in cell area, a decreased ability to form invadopodia, and a decreased percentage of polarized cells after 180 s of epidermal growth factor stimulation. Moreover, ADF KD or cofilin KD increased the rate of cell migration and the time of lamellipodia protrusion but through different mechanisms: lamellipodia protrude more frequently in ADF KD cells and are more persistent in cofilin KD cells. ADF KD cells showed a significant increase in F-actin aggregates, whereas cofilin KD cells showed a significant increase in prominent F-actin bundles and increased cell adhesion. Focal adhesion area and cell adhesion in cofilin KD cells were returned to control levels by expressing exogenous cofilin but not ADF. Return to control rates of cell migration in ADF KD cells was achieved by expression of exogenous ADF but not cofilin, whereas in cofilin KD cells, expression of cofilin efficiently rescued control migration rates.
  
  
  CONCLUSIONS
  Although ADF and cofilin have many redundant functions, each of these isoforms has functional differences that affect F-actin structures, cell adhesion and lamellipodial dynamics, all of which are important determinants of cell migration.
authors.affiliation: Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13115, Jordan. lubnatahtamuni@hu.edu.jo.
authors.forename: Lubna H
authors.initials: LH
authors.lastname: Tahtamouni
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Shaw
authors.forename: Maram H
authors.initials: MH
authors.lastname: Hasan
authors.forename: Salem R
authors.initials: SR
authors.lastname: Yasin
authors.forename: James R
authors.initials: JR
authors.lastname: Bamburg
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D051338:Cofilin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051345:Destrin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015972:Gene Expression Regulation, Neoplastic; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; C495812:Cfl1 protein, rat; D051338:Cofilin 1; D051345:Destrin; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor